A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of UTTR1147A Compared With Placebo and With Vedolizumab in Participants With Moderate to Severe Ulcerative Colitis (UC)

Genentech

Status and phase: Completed; Phase 2

Conditions: Ulcerative Colitis

Treatments: Drug: UTTR1147A; Drug: Vedolizumab; Drug: Vedolizumab Placebo; Drug: UTTR1147A Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03558152

GA39925

2017-002350-36 (EudraCT Number)

Details and patient eligibility

About

This study is designed to evaluate the efficacy, safety, and pharmacokinetics of UTTR1147A compared with vedolizumab and with placebo in the treatment of participants with moderate to severe UC. This study will consist of two parts, Part A and Part B. Part A will test the induction of clinical remission and Part B will test the durability of clinical remission.

Enrollment: 195 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of UC
• Confirmation of moderately to severely active UC, defined by the Mayo Clinic Score
• Inadequate response, loss of response, or intolerance to prior immunosuppressant treatment (i.e., azathioprine, 6-mercaptopurine, methotrexate, or tumor necrosis factor [TNF] inhibitors [maximum of 2 prior TNF inhibitors]) and/or corticosteroid treatment
• Use of highly effective contraception as defined by the protocol

Exclusion criteria

• History of psoriasis or psoriatic arthritis; any other inflammatory skin disorders requiring oral corticosteroids, immunosuppressants, or biological therapy within the previous year; or primary sclerosing cholangitis
• History of cancer as defined by the protocol
• Significant uncontrolled comorbidity, such as cardiac, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders (excluding UC)
• Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC
• Diagnosis of indeterminate colitis or granulomatous (Crohn's) colitis or toxic megacolon within 12 months prior to screening
• Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
• Current fistula or history of fistula, pericolonic abscess and stricture (stenosis) of the colon
• History or current evidence of unresectable colonic mucosal dysplasia or history of high-grade colonic mucosal dysplasia
• Prior treatment with UTTR1147A
• Prior treatment with vedolizumab, etrolizumab, natalizumab, efalizumab, or any other anti-integrin agents
• Prior treatment with rituximab
• Use of prohibited therapies, as defined by the protocol, prior to randomization
• Congenital or acquired immune deficiency
• Evidence or treatment of infections or history of infections, as defined by the protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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195 participants in 8 patient groups, including a placebo group

Arm 1a: UTTR1147A Dose Level 1 (Part A) + UTTR1147A (Part B)

Experimental group

Description:

Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.

Treatment:

Drug: Vedolizumab Placebo

Drug: UTTR1147A

Arm 1b: UTTR1147A Dose Level 1 (Part A) + Placebo (Part B)

Experimental group

Description:

Part A: UTTR1147A dose level 1 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo.

Treatment:

Drug: Vedolizumab Placebo

Drug: UTTR1147A Placebo

Drug: UTTR1147A

Arm 2a: UTTR1147A Dose Level 2 (Part A) + UTTR1147A (Part B)

Experimental group

Description:

Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.

Treatment:

Drug: Vedolizumab Placebo

Drug: UTTR1147A

Arm 2b: UTTR1147A Dose Level 2 (Part A) + Placebo (Part B)

Experimental group

Description:

Part A: UTTR1147A dose level 2 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo.

Treatment:

Drug: Vedolizumab Placebo

Drug: UTTR1147A Placebo

Drug: UTTR1147A

Arm 3a: UTTR1147A Dose Level 3 (Part A) + UTTR1147A (Part B)

Experimental group

Description:

Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A maintenance dose and Vedolizumab Placebo.

Treatment:

Drug: Vedolizumab Placebo

Drug: UTTR1147A

Arm 3b: UTTR1147A Dose Level 3 (Part A) + Placebo (Part B)

Experimental group

Description:

Part A: UTTR1147A dose level 3 and Vedolizumab Placebo. Part B: UTTR1147A Placebo and Vedolizumab Placebo.

Treatment:

Drug: Vedolizumab Placebo

Drug: UTTR1147A Placebo

Drug: UTTR1147A

Arm 4: Vedolizumab

Active Comparator group

Description:

Parts A and B: Vedolizumab and UTTR1147A Placebo.

Treatment:

Drug: Vedolizumab

Drug: UTTR1147A Placebo

Arm 5: Placebo

Placebo Comparator group

Description:

Parts A and B: UTTR1147A Placebo and Vedolizumab Placebo.

Treatment:

Drug: Vedolizumab Placebo

Drug: UTTR1147A Placebo